title: A systematically combined genotype and functional combination analysis of CYP2E1, CYP2D6, CYP2C9, CYP2C19 in different geographic areas of mainland China--a basis for personalized therapy.
abstract: The cytochrome P450 is the major enzyme involved in drug metabolism. Single CYP genotypes and metabolic phenotypes have been widely studied, but no combination analysis has been conducted in the context of specific populations and geographical areas. This study is the first to systematically analyze the combined genotypes and functional combinations of 400 samples of major CYP genes--CYP2E1, CYP2D6, CYP2C9, and CYP2C19 in four geographical areas of mainland China. 167 different genotype combinations were identified, of which 25 had a greater than 1% frequency in the Chinese Han population. In addition, phenotypes of the four genes for each sample were in line with the predictions of previous studies of the four geographical areas. On the basis of the genotype classification, we were able to produce a systemic functional combinations analysis for the population. 25 of the combinations detected had at least two non-wild phenotypes and four showed a frequency above 1%. A bioinformatics analysis of the relationship between particular drugs and multi-genes was conducted. This is the first systematic study to analyze genotype combinations and functional combinations across whole Chinese population and could make a significant contribution in the field of personalized medicine and therapy.
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China ; Shanghai geno mePilot Institutes for Genomics and Human Health, Shanghai, China.
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Wu
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Lu
authors.initials: L
authors.lastname: Shen
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Xiong
authors.forename: Xi
authors.initials: X
authors.lastname: Wu
authors.forename: Ran
authors.initials: R
authors.lastname: Huo
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Wei
authors.forename: Lei
authors.initials: L
authors.lastname: Cai
authors.forename: Guoyang
authors.initials: G
authors.lastname: Qi
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Xu
authors.forename: Daxiang
authors.initials: D
authors.lastname: Cui
authors.forename: Donghong
authors.initials: D
authors.lastname: Cui
authors.forename: Gengchun
authors.initials: G
authors.lastname: Zhao
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Shengying
authors.initials: S
authors.lastname: Qin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002681:China; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D005260:Female; D005838:Genotype; D005843:Geography; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D057285:Precision Medicine; D055815:Young Adult
chemical_list: C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6